SDMA as a marker and mediator in cerebrovascular disease DOI Creative Commons
Alexandra Riddell, Arun Flynn, Hugo Bergugnat

и другие.

Clinical Science, Год журнала: 2024, Номер 138(20), С. 1305 - 1323

Опубликована: Окт. 1, 2024

Abstract Symmetric dimethylarginine (SDMA) is a methylated derivative of arginine, generated by all cells as by-product cellular metabolism and eliminated via the kidney. For many years SDMA has been considered inert little biological significance. However, growing body evidence now suggests this view outdated that circulating levels may, in fact, be intricately linked to endothelial dysfunction vascular risk. In review, we specifically examine within context cerebrovascular disease, with particular focus on ischaemic stroke. We first discuss pre-clinical supporting notion effects nitric oxide signalling, inflammation, oxidative stress, HDL function. then appraise most recent clinical studies explore relationship between risk factors, such chronic kidney hypertension, atrial fibrillation, atherosclerosis, exploring whether any associations may arise due existence shared factors. Finally, consider elevated poor outcomes following haemorrhagic draw upon insights into function speculate how not only marker disease but could also directly influence pathology, highlight pressing need for more mechanistic alongside adequately powered, longitudinal fully evaluate marker/mediator disease.

Язык: Английский

Epigenetics-targeted drugs: current paradigms and future challenges DOI Creative Commons

Wanlin Dai,

Xinbo Qiao, Yuanyuan Fang

и другие.

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Ноя. 26, 2024

Epigenetics governs a chromatin state regulatory system through five key mechanisms: DNA modification, histone RNA remodeling, and non-coding regulation. These mechanisms their associated enzymes convey genetic information independently of base sequences, playing essential roles in organismal development homeostasis. Conversely, disruptions epigenetic landscapes critically influence the pathogenesis various human diseases. This understanding has laid robust theoretical groundwork for developing drugs that target epigenetics-modifying pathological conditions. Over past two decades, growing array small molecule targeting such as methyltransferase, deacetylase, isocitrate dehydrogenase, enhancer zeste homolog 2, have been thoroughly investigated implemented therapeutic options, particularly oncology. Additionally, numerous epigenetics-targeted are undergoing clinical trials, offering promising prospects benefits. review delineates epigenetics physiological contexts underscores pioneering studies on discovery implementation drugs. include inhibitors, agonists, degraders, multitarget agents, aiming to identify practical challenges avenues future research. Ultimately, this aims deepen epigenetics-oriented strategies further application settings.

Язык: Английский

Процитировано

34
Epigenetic Targets and Their Inhibitors in the Treatment of Idiopathic Pulmonary Fibrosis DOI

Xiaohui Miao,

Pan Liu, Yangyang Liu

и другие.

European Journal of Medicinal Chemistry, Год журнала: 2025, Номер 289, С. 117463 - 117463

Опубликована: Март 1, 2025

Язык: Английский

Процитировано

2
The Pivotal Role of Preclinical Animal Models in Anti-Cancer Drug Discovery and Personalized Cancer Therapy Strategies DOI Creative Commons

Haochuan Guo,

Xinru Xu,

Jiaxi Zhang

и другие.

Pharmaceuticals, Год журнала: 2024, Номер 17(8), С. 1048 - 1048

Опубликована: Авг. 9, 2024

The establishment and utilization of preclinical animal models constitute a pivotal aspect across all facets cancer research, indispensably contributing to the comprehension disease initiation progression mechanisms, as well facilitating development innovative anti-cancer therapeutic approaches. These have emerged crucial bridges between basic clinical offering multifaceted support investigations. This study initially focuses on importance benefits establishing models, discussing different types recent advancements in research. It then delves into treatment, studying characteristics stages tumor drugs. By integrating hallmarks we elaborate path drug provide guidance personalized therapy strategies, including synthetic lethality approaches novel drugs widely adopted field. Ultimately, summarize strategic framework for selecting safety experiments, tailored experimental modalities species, present an outlook prospects challenges associated with models. undoubtedly offer new avenues encompassing protocols. Nevertheless, road ahead continues be lengthy fraught obstacles. Hence, encourage researchers persist harnessing advanced technologies refine thereby empowering these emerging paradigms positively impact patient outcomes.

Язык: Английский

Процитировано

6
Structure, Function, and Activity of Small Molecule and Peptide Inhibitors of Protein Arginine Methyltransferase 1 DOI Creative Commons
Thordur Hendrickson-Rebizant, S Sudhakar, Michael J. Rowley

и другие.

Journal of Medicinal Chemistry, Год журнала: 2024, Номер 67(18), С. 15931 - 15946

Опубликована: Сен. 9, 2024

Protein arginine

Язык: Английский

Процитировано

6
Overview of PRMT1 Modulators: Inhibitors and Degraders DOI
Jun Wu,

Deping Li,

Li‐Fang Wang

и другие.

European Journal of Medicinal Chemistry, Год журнала: 2024, Номер 279, С. 116887 - 116887

Опубликована: Сен. 20, 2024

Язык: Английский

Процитировано

3
Roles of Lysine Methylation in Glucose and Lipid Metabolism: Functions, Regulatory Mechanisms, and Therapeutic Implications DOI Creative Commons
Zhen Wang, Huadong Liu

Biomolecules, Год журнала: 2024, Номер 14(7), С. 862 - 862

Опубликована: Июль 19, 2024

Glucose and lipid metabolism are essential energy sources for the body. Dysregulation in these metabolic pathways is a significant risk factor numerous acute chronic diseases, including type 2 diabetes (T2DM), Alzheimer’s disease (AD), obesity, cancer. Post-translational modifications (PTMs), which regulate protein structure, localization, function, activity, play crucial role managing cellular glucose metabolism. Among PTMs, lysine methylation stands out as key dynamic modification vital epigenetic regulation of gene transcription. Emerging evidence indicates that significantly impacts by modifying enzymes proteins. This review summarizes current understanding methylation’s regulatory mechanisms We highlight involvement methyltransferases (KMTs) demethylases (KDMs) generating abnormal signals affecting pathways. Additionally, we discuss chemical biology pharmacology KMT KDM inhibitors targeted degraders, emphasizing their clinical implications diseases such diabetes, neurodegenerative disorders, cancers. suggests targeting could be an ideal therapeutic strategy treating diseases.

Язык: Английский

Процитировано

2
Perspective for Drug Discovery Targeting SARS Coronavirus Methyltransferases: Function, Structure and Inhibition DOI
Xin Li, Yongcheng Song

Journal of Medicinal Chemistry, Год журнала: 2024, Номер 67(21), С. 18642 - 18655

Опубликована: Окт. 31, 2024

Severe acute respiratory syndrome-associated coronavirus 2 (SARS-CoV-2), the causative agent of disease 2019 (COVID-19), is highly contagious and caused a catastrophic pandemic. It has infected billions people worldwide with >6 million deaths. With expedited development effective vaccines antiviral drugs, there have been significantly reduced SARS-CoV-2 infections associated mortalities morbidities. The virus closely related to SARS-CoV, which emerged in 2003 several thousand higher mortality rate ∼10%. Because continued viral evolution drug-induced resistance, as well possibility new future, studies for therapies are needed. methyltransferases play critical roles SARS replication therefore promising drug targets. This review summarizes function, structure inhibition SARS-CoV. Challenges perspectives targeting treat discussed.

Язык: Английский

Процитировано

2
PRMT1 alleviates isoprenaline-induced myocardial hypertrophy by methylating SRSF1 DOI Creative Commons
Zi Yan,

Wenhui Zhao,

Naixin Zhao

и другие.

Acta Biochimica et Biophysica Sinica, Год журнала: 2024, Номер unknown

Опубликована: Сен. 29, 2024

Myocardial hypertrophy (MH) is an important factor contributing to severe cardiovascular disease. Previous studies have demonstrated that specific deletion of the protein arginine methyltransferase 1 (PRMT1) leads MH, but exact mechanism remains unclear. Serine/arginine-rich splicing (SRSF1) affects development and progression disease by selectively downstream signaling proteins. The present study designed determine whether PRMT1 involved in MH regulating SRSF1 and, if so, explore underlying mechanisms. Adult male mice H9C2 cardiomyocytes are treated with isoprenaline (ISO) establish models. expression levels significantly decreased ISO-induced models, inhibiting worsens whereas overexpression ameliorates MH. serves as target PRMT1, its markedly elevated Moreover, increases mRNA expressions CaMKIIδ A B, decreases C altering selective CaMKIIδ, further participates In addition, there interaction between SRSF1, whereby reduces phosphorylation level via methylation, thus functional activity eventually improving Our demonstrates relieves methylating which expected provide a new theoretical basis for pathogenic potential drug targets reducing associated

Язык: Английский

Процитировано

1
New insight into targeting the DNA damage response in the treatment of glioblastoma DOI
Tao Zhen, Tianyu Sun, Bin Xiong

и другие.

Chinese Journal of Natural Medicines, Год журнала: 2024, Номер 22(10), С. 869 - 886

Опубликована: Окт. 1, 2024

Язык: Английский

Процитировано

1
Methylation modification of non-histone proteins in breast cancer: An emerging targeted therapeutic strategy DOI Creative Commons
Mingyao Huang,

Zirong Jiang,

Yadan Xu

и другие.

Pharmacological Research, Год журнала: 2024, Номер 208, С. 107354 - 107354

Опубликована: Авг. 17, 2024

Breast cancer is a major public health concern worldwide, being the most commonly diagnosed among women and leading cause of cancer-related deaths. Recent studies have highlighted significance non-histone methylation in breast cancer, which modulates activity, interaction, localization, stability target proteins. This regulation affects critical processes such as oncogenesis, tumor growth, proliferation, invasion, migration, immune responses. review delves into enzymes responsible for methylation, protein arginine methyltransferases (PRMTs), lysine (KMTs), demethylases, explores their roles cancer. By elucidating molecular mechanisms functional consequences this aims to provide insights novel therapeutic strategies targeting these pathways. The potential overcome drug resistance enhance treatment efficacy also discussed, highlighting promising avenues future research clinical applications.

Язык: Английский

Процитировано

0